tbuckley/cabot-search huggingface dataset:
Inhaled anaesthesia and analgesia contribute to climate change
Authors: Jodi D Sherman, Brian B Chesebro
Journal: BMJ (2022)

We need clear targets and timelines for reducing emissions. The healthcare industry is a major contributor to harmful pollution, including nearly 5% of all global greenhouse gas emissions.1 With their core mission to support health and healing, all health professionals have a duty to prevent environmental pollution. Inhaled anaesthetics are a uniquely clinical source of greenhouse gases, making them of particular interest.2 Anaesthesiology has generated a large body of work assessing the emissions of these gases and developing mitigation solutions that do not compromise the quality or safety of patients (box 1).3 However, given their widespread use beyond the operating room, broader engagement is essential, including from professionals in maternity care, paediatrics, cardiology, emergency medicine, and veterinary medicine, as well as colleagues in facility engineering, administration, industry, and government. Box 1 ### Strategies for reducing inhaled anaesthetic pollution (adapted from Devlin-Hegedus et al3) #### Clinical practice #### Buildings #### Industry regulations and standardsRETURN TO TEXT
Brown Adipocyte ADRB3 Mediates Cardioprotection via Suppressing Exosomal iNOS
Authors: Jing-Rong Lin, Li-Li-Qiang Ding, Lian Xu, Jun Huang, Ze-Bei Zhang, Xiao-Hui Chen, Yu-Wen Cheng, Cheng-Chao Ruan, Ping-Jin Gao
Journal: Circulation Research (2022)

The ADRB3 (β3-adrenergic receptors), which is predominantly expressed in brown adipose tissue (BAT), can activate BAT and improve metabolic health. Previous studies indicate that the endocrine function of BAT is associated with cardiac homeostasis and diseases. Here, we investigate the role of ADRB3 activation-mediated BAT function in cardiac remodeling.BKO (brown adipocyte-specific ADRB3 knockout) and littermate control mice were subjected to Ang II (angiotensin II) for 28 days. Exosomes from ADRB3 antagonist SR59230A (SR-exo) or agonist mirabegron (MR-exo) treated brown adipocytes were intravenously injected to Ang II-infused mice.BKO markedly accelerated cardiac hypertrophy and fibrosis compared with control mice after Ang II infusion. In vitro, ADRB3 KO rather than control brown adipocytes aggravated expression of fibrotic genes in cardiac fibroblasts, and this difference was not detected after exosome inhibitor treatment. Consistently, BKO brown adipocyte-derived exosomes accelerated Ang II-induced cardiac fibroblast dysfunction compared with control exosomes. Furthermore, SR-exo significantly aggravated Ang II-induced cardiac remodeling, whereas MR-exo attenuated cardiac dysfunction. Mechanistically, ADRB3 KO or SR59230A treatment in brown adipocytes resulted an increase of iNOS (inducible nitric oxide synthase) in exosomes. Knockdown of iNOS in brown adipocytes reversed SR-exo-aggravated cardiac remodeling.Our data illustrated a new endocrine pattern of BAT in regulating cardiac remodeling, suggesting that activation of ADRB3 in brown adipocytes offers cardiac protection through suppressing exosomal iNOS.
Outcome and surveillance pattern in older GIST population.
Authors: Thanh P. Ho, Brittany L Siontis, Cornelius A Thiels, Travis Edward Grotz, Scott H. Okuno, Steven Ian Robinson
Journal: Journal of Clinical Oncology (2022)

e24016 Background: Recent studies of patients (pts) with gastrointestinal stromal tumor (GIST) have included an older patient population. The majority of these have focused on treatment, but little is known regarding the optimal duration of surveillance following surgery for localized disease. Methods: We conducted a retrospective study of pts age 70 years (yrs) and above (≥) at diagnosis (dx), who underwent surgery for their localized GIST. Charts were reviewed of GIST diagnosed between 1992 to 2016, to allow at least 5 yrs for surveillance, if performed. Demographics were analyzed and pts were risk stratified using modified NIH criteria. Results: We identified 42 pts with a median age of 74 yrs (70 to 89 yrs) at dx. The majority of pts were male (31, 74%) and non-Hispanic White (37, 88%). Most pts had gastric GIST (25, 60%). The median resected tumor was 47 mm (range 6 to 190). Thirty-nine of 42 pts had margin status documented R0 resection. The median overall survival for all pts was 7.9 yrs (1.1 to 17.7), with median recurrence free survival 5.6 yrs (1.1 to 13.7). Only 4 of 16 (25%) pts died from GIST recurrence, and all were detected under 5 yrs from surgery. Fourteen of 34 pts (41%) who survived over 5 yrs from resection had extended surveillance imaging. Demographics and risk stratification are shown in Table. None of the 16 low risk pts developed recurrence, including 6 (38%) whose surveillance imaging continued beyond 5 yrs. Among 7 intermediate risk pts, only 1 pt (14%) extended surveillance imaging beyond 5 yrs. Two intermediate risk pts (29%) developed recurrence and were symptomatic at dx. One intermediate risk pt died from GIST metastasis within 1 yr from surgery. Seven of 19 (37%) high risk pts had surveillance imaging beyond 5 yrs following surgical resection. Seven high risk pts (37%) developed recurrence within median 5.6 yrs (1.6 to 13.7) from surgery; five of these were detected on imaging. In the high risk pts with recurrence, 5 had received adjuvant imatinib and 2 declined any systemic therapy. Three pts (16%) in the high risk cohort died from GIST. Conclusions: In this cohort of pts age ≥ 70 yrs with resected GIST, the majority of pts were symptomatic at relapse. Older pts who undergo surgery for low risk GIST may not require extended surveillance. Fit, older pts with high risk GIST may benefit from extended surveillance imaging, even if they received adjuvant imatinib.[Table: see text]
Dynamics of Methylation of <scp>CpG</scp> Sites Associated With Systemic Lupus Erythematosus Subtypes in a Longitudinal Cohort
Authors: Cristina M. Lanata, Joanne Nititham, Kimberly E. Taylor, Olivia Solomon, Sharon A. Chung, Ashira Blazer, Laura Trupin, Patricia Katz, Maria Dall'Era, Jinoos Yazdany, Marina Sirota, Lisa F. Barcellos, Lindsey A. Criswell
Journal: Arthritis & Rheumatology (2022)

Findings from cross-sectional studies have revealed associations between DNA methylation and systemic lupus erythematosus (SLE) outcomes. This study was undertaken to investigate the dynamics of DNA methylation by examining participants from an SLE longitudinal cohort using samples collected at 2 time points.
Hypoxia-inducible factors: roles in cardiovascular disease progression, prevention, and treatment
Authors: Gregg L Semenza
Journal: Cardiovascular Research (2022)

Hypoxia-inducible factors (HIF)-1 and HIF-2 are master regulators of oxygen homeostasis that regulate the expression of thousands of genes in order to match O2 supply and demand. A large body of experimental data links HIF activity to protection against multiple disorders affecting the cardiovascular system: ischemic cardiovascular disease (including coronary artery disease and peripheral artery disease), through collateral blood vessel formation and preconditioning phenomena; emphysema; lymphedema; and lung transplant rejection. In these disorders, strategies to increase the expression of one or both HIFs may be of therapeutic utility. Conversely, extensive data link HIFs to the pathogenesis of pulmonary arterial hypertension and drugs that inhibit one or both HIFs may be useful in treating this disease.
Apatinib combined with chemotherapy versus single chemotherapy in HER-2 negative advanced breast cancer: A randomized, controlled, open-label phase II study.
Authors: Zhanhong Chen, Xiaojia Wang, Jian Huang, Yabing Zheng, Xiying Shao, Wenming Cao, Junqing Chen, Weiwu Ye, Huang Ping, Guangliang Li, Lei Lei, Lei Shi, Yuan Huang, Weibin Zou, Rong Wang, Xia-Bo Shen, Caijin Lou
Journal: Journal of Clinical Oncology (2022)

1072 Background: Apatinib is an oral, highly potent tyrosine-kinase inhibitor targeting VEGFR2. A series of clinical studies have shown that anti-angiogenic drugs combined with chemotherapy enable to improve the efficacy of HER2-negative advanced/metastatic breast cancer(MBC). Methods: Patients with HER2-negative MBC with less than two lines of systemic therapy were enrolled in this open-label, controlled, phase II trial. Patients with measurable disease were randomly assigned, in a 1:1 ratio, to receive oral apatinib (250 mg once daily) combined with chemotherapy(A+CT) or chemotherapy(CT) alone (the physician’s choice) until disease progression or intolerable toxicity. The primary end point was progression-free survival(PFS), which was assessed by investigator and was analyzed on an intention-to-treat basis. Results: Between August 2017 and January 2021, of the 80 patients who underwent randomization, 40 were assigned to receive apatinib plus chemotherapy(A+CT) and 40 were assigned to receive standard therapy(CT). As of January 2022, 10 patient had not undergone response evaluation or dropout, 70 patients(36 patients in A+CT, 34 patients in CT were finally included with PFS events and 72 patients were included in safety set. Median PFS was significantly longer in A+CT than in CT (182 days vs 63 days; P = 0.043);The median PFS of TNBC subgroup (11 in A+CT group, 14 in CT) was longer in the aptinib group than in CT group (167 days vs 63 days; P = 0.637);The median PFS of HR+ subgroup(25 in apatinib group, 20 in chemotherapy group) was longer in the aptinib group than in CT group (259 days vs 56 days; P = 0.054);The median PFS of patients with liver metastases(19 in apatinib group, 17 in chemotherapy group) was longer in the aptinib group than in the CT group (151 days vs 54 days; P = 0.191); The severe adverse reactions (grade 3/4) were neutropenia(22.2% vs 13.9%), hypertension(11.1% vs 0.0%), leukopenia(8.3% vs 8,3%), hypokalemia(8.3% vs 2.8%), anemia(5.6% vs 11.1%), ALT(2.8% vs 8.3%), AST(0.0% vs 5.6%) in the apatinib group and the CT, respectively. Proteinuria did not occur in both groups. Treatment delay or dose reduction owing to adverse event was 16.7% and 11.1%, respectively. Treatment discontinuation owing to adverse event was 23.5% and 8.8%, respectively. Conclusions: Apatinib combined with chemotherapy showed a significant improvements in PFS and a manageable safety profile in HER2 negative MBC.
Climate change and cardiovascular disease: implications for global health
Authors: Haitham Khraishah, Barrak Alahmad, Robert L. Ostergard, Abdelrahman AlAshqar, Mazen Albaghdadi, Nirupama Vellanki, Mohammed M. Chowdhury, Sadeer G. Al-Kindi, Antonella Zanobetti, Antonio Gasparrini, Sanjay Rajagopalan
Journal: Nature Reviews Cardiology (2022)
Actionability of comprehensive genomic profiling (CGP) compared to single-gene and small panels in patients with advanced/metastatic non-small cell lung cancer (aNSCLC): A real-world study.
Authors: Bela Bapat, Connor Sweetnam, Ashleigh McBratney, Monika A. Izano, Brock Schroeder, Sheetal Walters, William Chen, Phillip G. Febbo, Anna B. Berry
Journal: Journal of Clinical Oncology (2022)

e21114 Background: Biomarker testing for patients with aNSCLC includes testing for specific alterations in single genes, hotspot multigene panels, or CGP. Historically, CGP has been used following progression on early lines of systemic therapy to identify genomic alterations not captured by single-gene/hotspot testing, or to determine clinical trial(CT) eligibility. We compared the proportion of patients with genomic alterations for which FDA has approved targeted therapies(TT) (actionable alterations) identified through CGP vs. single-gene/small panel(“small panel”) testing in the real-world setting. Methods: In a retrospective study, patients initially diagnosed-with/progressed-to aNSCLC between 1/1/2015-12/31/2020, treated in the US community health setting, were categorized based on small panel or CGP testing. Patients were followed until the earliest of last contact/death/study-end on 9/30/2021. Testing between 30 days prior to initial NSCLC diagnosis and end of follow-up was used to determine actionability based on OncoKB levels, and eligibility for two basket-CTs(ASCO-TAPUR, NCI-MATCH). Results: Of 7,242 aNSCLC patients in this study, 5,154 (72%) received molecular testing (50% only small panel; 14% CGP; and 7% with an unknown size panel), 22% of patients remained untested and 7% were tested for only PD-L1. Among CGP-tested patients evaluated for tumor mutational burden (TMB), 18% were classified as TMB-High. &gt; 75% of patients presented with advanced cancer at initial diagnosis, 51% were female, 50% were White, and median age was 68 years. Molecular testing rate increased from 9% to 20%(CGP) and 42% to 51%(small panel) between 2015–2020. The proportion of patients with ≥1 actionable biomarker was significantly higher with CGP than small panels (34%vs.15%; p &lt; 0.001). Of tested patients. the proportion of CT eligible patients was also significantly greater for CGP than small panels (56%vs.4%; p &lt; 0.001). The proportion of tested patients that received an FDA-approved TT or immunotherapy(IO) within 30 days of testing was higher in CGP cohort compared to small panel (9%vs.3%; p &lt; 0.001). Conclusions: Although rates of CGP and small panel testing are increasing over time, overall molecular testing remains underutilized, and the proportion of patients who received TT/IO post-testing is low. Use of CGP is associated with higher identification of actionable biomarkers and patients receiving TT/IO, and CT eligibility.
DNA methylation aberrations predicts recurrence both in tumor and normal appearing prostate tissue
Authors: C. Pedersen, E. Midtbust, S. Krossa, M.K. Andersen, T. Viset, Ø. Størkersen, G.F. Giskeødegård, M.B. Rye, M-B. Tessem
Journal: European Urology (2022)
Chemo or chemo-free regimens in heavily pretreated multiple myeloma? Role of bendamustine-bortezomib-dexamethasone (BVD) in NOVEL agents' era.
Authors: Claudio Cerchione, Lucio Catalano, Davide Nappi, Sonia Ronconi, Delia Cangini, Michela Ceccolini, Gerardo Musuraca, Giovanni Martinelli
Journal: Journal of Clinical Oncology (2022)

e20010 Background: The treatment of heavily pretreated Multiple Myeloma continues to be considered as an important unmet clinical need. Bendamustine is an old bi-functional alkylating agent which has proved to be effective in relapsed, refractory and in new diagnosed Multiple Myeloma (MM). Thus, aiming to provide further insights in this field, also in novel agents’era, we present here a retrospective, real-life analysis of patients with relapsed/refractory MM (rrMM), who had received salvage therapy with bendamustine in combination with bortezomib and dexamethasone (BVD). Methods: 81 patients (44 M/37 F), with rrMM, median age at diagnosis 59.4 years (r. 36-82), median age at start of treatment 63.6 years (r.37-86) treated with several lines of treatments (median 6, r. 2-11), every refractory to all the drugs previously received (also Bortezomib), received BVD (B 90 mg/sqm days 1,2; V 1.3 mg/sqm days 1,4,8,11, D 20 mg days 1,2,4,5,8,9,11,12, Pegfilgrastim day +4) every 28 days, until progression. All patients had previously received bortezomib-based and IMIDs-based treatments, and 32% (26/81) had also received radiotherapy. 69% (56/81) had undergone single or double autologous and three (2%) allogeneic stem cell transplant. All patients were relapsed and refractory to last therapies received before BVD. Results: Bendamustine was well tolerated, with grade 3-4 transfusion-dependent anemia in 56% (46/81) of patients, and 43% (35/81) grade 3-4 neutropenia (no ospedalization was required, no septic shocks were observed). No severe extrahematologic toxicity was observed, only grade 1 gastrointestinal side effect (nausea), treated by common antiemetic drugs. According to IMWG, ORR was 63% (51/81: 7 CR, 18 VGPR, 15 PR, 11 MR) with 11 PD and 19 patients in SD, which can be considered as an impressive result in this subset of rrMM patients. In particular, for 11 patients, BVD was, after having achieved at least a PR, a bridge to second auSCT, and for two patients a bridge to alloSCT. Eight patients have surprisingly achieved a notable PR after failure of novel agents (i.e. Carfilzomib, Daratumumab and Pomalidomide). Median time to response was 1.3 months (r.1-3), median OS from diagnosis was 67.3 months (r.6-151), median OS from start of Bendamustine was 9.6 months (r.2-36). Conclusions: The triplet Bendamustine-Bortezomib-Dexamethasone has shown significant efficacy in a particularly severe setting of patients, relapsed and refractory to all available therapeutic resources, and, in particular cases, it could be considered as a bridge to a second autologous or allogenic SCT, also after failure of novel agents. Clinical trial information: A101.
Tumor neutrophil extracellular traps and pretreatment neutrophils in association with progression-free survival in patients with metastatic non-small cell lung cancer receiving pembrolizumab alone or with chemotherapy.
Authors: Mila Petrova, Dimiter Parvanov, Rumiana Ganeva, Dimiter Metodiev, Svitlana Bachurska, Mariyana Eneva, Polya Penkova, Teodor Popov, Krasimir Nikolov, Margarita Taushanova, Petya Kraleva, Rossitza Krasteva Ruseva, Kiril Zhelev, Ivan Donev
Journal: Journal of Clinical Oncology (2022)

e21099 Background: Background: In this multicentric retrospective study, we evaluated the relationship between pre- treatment blood neutrophils and neutrophil extracellular traps (NET) in biopsy samples and their predictive value for progression progression-free survival (PFS) in patients with non-small-cell lung cancer (NSCLC) receiving immunotherapy alone or in combination with chemotherapy as a first-line treatment. Methods: Patients with metastatic NSCLC (n = 100) were retrospectively analyzed between Apr 2018 and Sep 2021; 77.5% of the patients received platinum-containing chemotherapy with Pembrolizumab, and 22.5% – Pembrolizumab only as a first-line treatment. Pre-treatment blood neutrophils were counted. Tissue sections were stained immunohistochemically for Neutrophil elastase (NE) and Histone H3. Both NE and Histone H3 stained tissue areas were calculated manually and determined by Image-J software. We considered the extracellular components that were double-positive for NE and H3 to be NET. Results: In correspondence analysis, patients with low levels (&lt; 33 rd percentile) of pre-treatment neutrophils were grouped with low amounts (&lt; 33 rd percentile) of NET-positive tumor areas (p = 0.02). The amounts of NET-positive tumor areas were not related to other clinicopathological characteristics of the patients. Patients with an intermediate/high amount of NET-positive areas had significantly shorter mean PFS, 10.7 (95% CI: 9.6–11.8) than those with low NET-positive areas, 14.8 (95% CI: 11.5–18.1) (log-rank test p = 0.003). Moreover, in a multivariate Cox regression model, the presence of an intermediate/high amount of NET-positive areas was an independent predictive factor for shorter PFS, HR 2.1 (95% CI: 1.2–3.7; p = 0.005). Conclusions: Our study suggests that tumor formation of NETs is related to the numbers of pre-treatment neutrophils and may mediate neutrophil-induced antitumor resistance. Excessive NET formation in tumor tissue is a potential negative predictive marker for shorter PFS.
Deleterious effect of serum from stemi patients on endothelial cell viability: implication on the resulting cardiac structure
Authors: C Rios Navarro, E De Dios, J Gavara, N Perez-Sole, V Marcos-Garces, FJ Chorro, A Ruiz-Sauri, V Bodi
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by “Instituto de Salud Carlos III” and “Fondos Europeos de Desarrollo Regional FEDER” (grant numbers PI20/00637 and CIBERCV16/11/00486) and Conselleria de Educación – Generalitat Valenciana (PROMETEO/2021/008). Aim To evaluate the potential deleterious effect of serum from STEMI patients on cardiovascular magnetic resonance (CMR)-derived edema, hemorrhage and microvascular obstruction as well as on the grade of permeability in vitro by promoting endothelial cell apoptosis and necrosis in vitro. Methods Human coronary artery endothelial cells (HCAEC) were incubated with serum isolated 24h post-reperfusion from 43 STEMI patients submitted to CMR and from 10 control subjects. Using a multidisciplinary approach on HCAEC, the effect of serum from STEMI patients on the activation of apoptosis and necrosis as well as on changing the permeability and structure of the endothelial monolayer was assessed. The association between the serum-induced apoptosis and necrosis in vitro on HCAEC and CMR-derived edema, hemorrhage, and microvascular obstruction as well as the grade of permeability in vitro was also dissected. Results Serum from STEMI patients activated apoptosis (p&amp;lt;0.01) and necrosis (p&amp;lt;0.05) in HCAEC, evaluated by flow cytometry, enzymatic, genetic, and morphological analysis, and also provoked an increased in the permeability of the endothelial monolayer in vitro (p&amp;lt;0.01), due to enlarged intercellular spaces (p&amp;lt;0.05). Those patients whose serum induced higher necrosis in vitro displayed extensive CMR-derived edema (p&amp;lt;0.01), hemorrhage (p&amp;lt;0.01), and microvascular obstruction (p&amp;lt;0.05) as well as more endothelial permeability in vitro (p&amp;lt;0.05). Conclusions By activating apoptosis and necrosis on endothelial cells, serum from STEMI patients participates in the appearance of edema, hemorrhage, and microvascular obstruction as well as in increasing endothelium permeability. The negative effect of serum on the endothelial barrier can contribute to the adverse cardiac structure post-STEMI.
[18F]-FDG PET/CT for bladder cancer staging and decision-making in patients with High-Risk Non-Muscle Invasive Bladder Cancer (HR-NMIBC)
Authors: R. Hurle, A. Gobbo, P. Casale, A. Saita, N. Buffi, G. Lughezzani, M. Sollini, M. Rodari, C. Pini, F. Gelardi, R. Contieri, G. Guazzoni, A. Chiti, M. Lazzeri
Journal: European Urology (2022)